To provide support for Clinical Research in the Department of Neurology

Research

Welcome to the Department of Neurology

Principal Investigators A-B

Enrique Alvarez, MDDr. Alvarez’s research interests include optimizing treatment decisions for patients with multiple sclerosis and related diseases and especially in clinical studies involving immunotherapies for the treatment of this disease. Additionally, Dr. Alvarez is interested in biomarkers to improve treatment decisions and diagnosis of neuroimmunological diseases.

Al (Clarke) Anderson, MDDr. Anderson’s research is focused on stroke prevention and the cognitive and emotional effects of stroke. He assesses neurobehavior in patients with focal cerebrovascular lesions and vascular dementia.

Jeffrey L. Bennett, MD, PhDOptic Neuritis. Optic neuritis (ON) is the most common clinically-isolated demyelinating syndrome, and is the presenting feature in approximately 25% of individuals with multiple sclerosis (MS). Dr. Bennett is attempting to identify the primary target of the humoral immune response in ON and MS. His laboratory utilizes a RT-PCR protocol to amplify the expressed variable-region sequences of single B-lymphocytes and plasma cells isolated from ON CSF by fluorescence-activated cell sorting. The B-lymphocyte and plasma cell heavy- and light-chain pairings found in vivo are reconstituted in vitro to produce a panel of recombinant monoclonal antibodies (mAbs) whose specificity is determined by immunocytochemistry, immunoblotting, and screening of white matter and random peptide expression libraries. Since many patients with ON do not develop MS, these studies will allow identification of clinical and molecular risk factors that may point to the ultimate cause of human demyelinating disease and allow physicians to identify at-risk individuals, to diagnose MS at the earliest stage of disease and to treat patients with therapies designed to modify or even cure disease.

Brian D. Berman, MDDr. Berman uses structural and functional imaging techniques to study the underlying pathophysiology of movement disorders including Parkinson disease (PD) and dystonia. His current research projects involve the use of diffusion tensor imaging (DTI) and functional connectivity MRI (fMRI) to investigate the changes that occur within basal ganglia circuits in PD and dystonia patients. Knowledge gained from these investigations will help us better understand the pathophysiology that underlies the heterogenous clinical symptoms seen in these disorders. The ultimate goal of these projects is to develop and validate neuroimaging biomarkers for these diseases that will aid in their diagnosis and inform treatment development. He is also is a lead site investigator for a natural history and biorepository project in focal dystonia funded by the NIH Rare Diseases Clinical Research Network.

Marius Birlea, MDIt is known that the alphaherpesviruses (herpes simplex 1 and 2 and varicella-zoster virus) can be associated with headache as a manifestation of systemic or intracranial infection, with or without vesicular rash. Dr. Birlea’s research interest regards the extent to which subclinical reactivation of alphaherpesviruses may be involved in head pain conditions, including primary headaches like migraine. Proposed scientific approaches include detecting salivary biomarkers and epidemiological studies. Dr. Birlea is also interested in studing the relationship between migraine and inflammation and the populational headache impact.

Patrick J. Bosque, MDDr. Bosque’s research is directed at chronic wasting disease, Creutzfeldt-Jakob disease and other prion disorders of human and animals. Dr. Bosque also studies the role of protein misprocessing in various neurodegenerative diseases.

Mesha-Gay Brown, MDDr. Brown's training in clinical epilepsy and biomedical research represents her clinical research goals of improving the localization of epileptic networks for surgery and devices as a treatment of epilepsy. She believes that improved localization will enable epileptologists to better assign individual patients to the best individualized therapy, whether that is seizure control devices, resective surgery, or continued medical therapy. She has also been involved with clinical trials for epilepsy.

Mark P. Burgoon, PhDDr. Burgoon’s research investigates the unknown etiology of multiple sclerosis (MS) by examining the humoral immune response in the CNS of MS patients. The persistence of increased IgG in the brains and CSF of MS patients, observed as intrathecally synthesized oligoclonal bands, suggests a continuous antigen-driven immune response. The IgG response in the brain and CSF MS patients is being dissected to determine the antigenic targets in archival acute plaques. These unbiased studies of the intrathecal humoral response can potentially identify an antigen in MS and ultimately the cause of disease. Dr. Burgoon’s laboratory also uses recombinant antibodies and biopanning techniques to analyze molecular features of the IgG response in subacute sclerosing panencephalitis (SSPE), a proof of principle model in which the antigen-driven humoral response is directed against measles virus, the cause of the disease.

Principal Investigators C-F

Penny Clarke, PhDVirus-induced diseases of the central nervous system (CNS), including the brain (encephalitis) and spinal cord (myelitis) induce significant morbidity and mortality throughout the world. Treatments for these diseases are sub-optimal or non-existent. Dr. Clarke’s laboratory uses clinically important viral pathogens (West Nile virus, Japanese encephalitis virus and herpes simplex virus) to investigate cellular genes and signaling pathways that are up-regulated or activated in the CNS following virus infection and to evaluate these host factors as therapeutic targets for virus-induced CNS disease. Dr. Clarke’s research has identified apoptosis as a key mechanism of virus-induced pathology within the CNS and interferon signaling as a critical component of anti-viral defenses. Dr. Clarke’s research has also demonstrated the generation of a robust neuroinflammatory response in the CNS following virus infection, including the activation of resident immune cells (astrocytes and microglia) and the up-regulation of pro-inflammatory gene expression. The role of this response in viral pathology is currently being investigated.

Randall J. Cohrs, PhDVaricella zoster virus (VZV) is a ubiquitous neurotropic alphaherpesvirus that typically causes childhood chickenpox, becomes latent in cranial nerve, dorsal root and autonomic nervous system ganglia, and reactivates during a declining T-cell response to produce shingles. Dr. Cohrs studies the molecular mechanism by which VZV latency is established and maintained, and the steps involved in virus reactivation. Dr. Cohrs’ laboratory uses state-of-the-art techniques including genomics (expression microarrays) and proteomics (protein identification) as well as more standard cDNA analysis by RT-PCR to investigate the state of virus transcription in latently infected human ganglia. After latently transcribed VZV genes have been identified, their regulation and function of the encoded protein is analyzed. A more complete understanding of virus latency will aid in development of steps to prevent virus reactivation.

John R. Corboy, MDDr. Corboy's research involves immunotherapies for multiple sclerosis (MS) patients. These studies look at novel, still unapproved agents, as well FDA approved therapies in novel settings. He is the Director of the Rocky Mountain MS Center Tissue Bank, one of the world’s largest MS-specific banks, providing MS tissues to researchers all over the world. In collaboration with others on campus, he also studies biomarkers of disease activity in MS.

Denise M. Damek, MDDr. Damek’s clinical research interest focuses on experimental drug therapy of CNS tumors. Ongoing clinical trials in the neuro-oncology program include investigation of novel drugs, new combinations of chemotherapy agents, innovative approaches of radiation therapy, and immunotherapy.

Cornelia Drees, MDDr. Drees is involved in several quality improvement projects within the epilepsy division. In one project, she is investigating factors affecting treatment of status epilepticus in the hospital. She is also interested in improving access and outcomes in epilepsy surgery.

Christopher M. Filley, MDDr. Filley has conducted research in many areas of behavioral neurology, including the dementias, traumatic brain injury, focal neurobehavioral syndromes, and neuropsychiatric disorders. Early in his career he participated in many observational studies and clinical trials in Alzheimer's Disease, and since 2006 he has organized research projects within the Alzheimer’s Disease and Cognition Center (ADCC) on functional MRI of normal cognition, early diagnosis of Alzheimer’s Disease with functional MRI, and diffusion tensor imaging studies of fragile X tremor ataxia syndrome. Throughout his career, the unifying theme of Dr. Filley's research has been the behavioral neurology of white matter, as manifested by a wide range of disorders such as toluene leukoencephalopathy, multiple sclerosis, and systemic lupus erythematosus. He has formally proposed the concept of white matter dementia to call attention to and characterize cognitive dysfunction attributable to white matter involvement, described in his book The Behavioral Neurology of White Matter, now in its second edition.

Lauren C. Frey, MDDr. Frey is interested in the processes of the development of epilepsy after traumatic brain injury. Only about 20% of people who survive severe traumatic brain injury will develop epilepsy. Developing tools to predict which survivors will develop epilepsy offers clues about the changes in brain structure necessary for the occurrence of epilepsy. It will also allow physicians to identify, and aggressively treat, TBI survivors at highest risk of developing epilepsy in hopes of preventing seizures altogether. Dr. Frey is a Faculty Associate of the Colorado Injury Control Research Center and a Faculty Affiliate in the University of Colorado’s graduate Neurosciences Program.

Vera Fridman, MDDr. Fridman’s research interests focus of identifying therapies for hereditary nerve disorders (also known as Charcot Marie Tooth Disease). Additionally, she is interested in identifying new forms of hereditary neuropathy and in defining biomarkers that can be used to measure progression in these disorders over time.

Principle Investigators G-M

Donald H. Gilden, MDVaricella Zoster Virus/Simian Varicella Virus. The neurovirology laboratory studies the physical state of varicella zoster virus (VZV) nucleic acid and viral gene expression during latency in human ganglia. Studies include state-of-the-art technologies such as polymerase chain reaction, cDNA preparation and microarray to analyze VZV transcription.Interaction of VZV proteins with other virus and cellular proteins are also being examined. In parallel, a model system of varicella in primates produced by simian varicella virus (SVV) is used to study pathogenesis and latency. Finally, the neurovirology laboratory uses diagnostic tests to understand and treat the neurological complications of zoster, including postherpetic neuralgia and other complications ofVZV reactivation such as myelopathy and vasculopathy.

Multiple Sclerosis. Dr. Gilden directs the multiple sclerosis (MS) laboratory. His laboratory uses molecular immunology techniques to determine the cause of MS. Cutting-edge methodologies have been developed to examine the antigenic targets of the IgG antibody present in MS brain and CSF. The techniques include single cell PCR to identify IgG sequences utilized in MS brains, synthetic antibody production, and phage-displayed library panning to isolate high-affinity antibodies and antigens from brain. Subacute sclerosing panencephalitis (SSPE) is being used as an experimental paradigm to demonstrate these new techniques and to develop the sensitivity required for studies of MS.

Carol Hennessy, MSMMs. Hennessy has participated as a study coordinator and sub-investigator in studies of stroke treatment and Parkinson’s disease. She is interested in integrative approaches to chronic illness and would like some day to engage in research in this area.

Richard L. Hughes, MDDr. Hughes has participated in multiple clinical trials on acute stroke resuscitation, secondary prevention of stroke and the detection of intracranial aneurysms. Current trials include treatment of intracerebral hemorrhage with activated Factor VII, the use of warfarin and aspirin in heart failure, and treatment of insulin resistance to reduce stroke. He works with the Colorado Department of Heath and Environment to establish a statewide registry to help design and implement a statewide stroke system in Colorado.

Leila J. Jackson, PhDIn the past few years, several new efficacious therapies have emerged for treatment of patients with neuroimmunological disorders such as Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO). Dr. Jackson’s research lab focuses on the mechanisms of action of these therapeutics, as well as discovering potential novel therapies for patients with neuroimmunological disorders including MS, NMO and others. This lab researches immune mechanisms mediating neurological disorders to further understand how immune cells orchestrate disease initiation, progression, stability, and remission. Dr. Jackson studies innate and adaptive human immune cells and their ability to communicate with (activate or repress) cells within the brain and central nervous system in the context of disease. The results from these studies will potentially lead to a better understanding of the current and emerging therapies in neuroimmunological disorders providing rationale for combination therapies or novel therapeutics for effected patient populations.

Olga S. Klepitskaya, MDDr. Klepitskaya’s research interests include surgical treatment for movement disorders, specifically Deep Brain Stimulation (DBS), and behavioral aspects of Parkinson’s disease (PD), such as Dopamine Dysregulation Syndrome, cognitive and behavioral outcomes after DBS. She is involved in clinical trials of new medications and new types of surgical treatments for PD and other movement disorders.

Benzi M. Kluger, MD, MS Dr. Kluger’s research involves the application of neuropsychological testing, transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) to understand the pathophysiology of the non-motor symptoms of movement disorders and other neuropsychiatric illnesses. His research currently focuses on understanding the neurophysiologic basis of fatigue, particularly as it affects patients with Parkinson’s disease. Other interests of Dr. Kluger include behavioral neurology, volitional action and conscious perception.

Pearce J. Korb, MDDr. Korb’s research interests include areas of clinical epilepsy specifically the use of continuous electroencephalogram (EEG) monitoring in critically ill patients and the use of advanced imaging techniques (e.g., PET quantification, SPECT analysis, DTI, etc.) for identification of epileptogenic zones as potential targets for epilepsy surgery. He has also been involved with clinical trials for epilepsy. His other areas of research interest include quality improvement for inpatient evaluation and management of neurological emergencies including status epilepticus.

Maureen A. Leehey, MDDr. Leehey studies the etiology and treatment of neurodegenerative disease. She and her collaborators recently discovered the fragile X-associated tremor/ataxia syndrome (FXTAS), which affects about 1 in 10,000 men over age 50, especially grandfathers of children with fragile X syndrome. While Dr. Leehey’s major research effort is to characterize FXTAS, she directs multiple clinical trials designed to offer novel medical therapy and to uncover the etiology and genetics of various movement disorders, especially Parkinson disease. Dr. Leehey collaborates closely with basic scientists to translate their efforts into meaningful interventions. She and her colleagues recently uncovered the genetic etiology (a prion mutation) of a large family with a rare neurodegenerative disease. Her efforts are funded by the National Institutes of Health, Michael J. Fox Foundation, and other governmental and private agencies.

Teerin Liewluck, MDMuscular dystrophies and non-inflammatory myopathies are genetically heterogeneous disorders primarily affecting skeletal muscle, which lead to progressive muscle weakness and some extramuscular problems. Myofibrillar myopathies are a group of muscular dystrophies that share the common pathological features of early myofibrillar degeneration. Dr. Liewluck is interested in the heterogeneity and complexity of genetic basis of these primary muscle disorders. Dysferlinopathy is a muscular dystrophy caused by mutations in dysferlin-encoding gene (DYSF). DYSF mutations were reported to cause amyloid myopathy without systemic amyloidosis (isolated amyloid myopathy). He and his former mentor, Dr. Margherita Milone, have recently described a novel form of isolated amyloid myopathy due to ANO5 mutations. ANO5 mutations were previously reported to cause limb-girdle and distal muscular dystrophies.

Neuromuscular hyperexcitability syndromes are a group of neuromuscular disorders due to hyperexcitable nerves or muscles. Patients typically present with myalgia, muscle cramps or muscle stiffness accompanied by involuntary muscle twitching. Neuromuscular hyperexcitability disorders include rippling muscle disease (RMD) and various peripheral nerve hyperexcitability (PNH) syndromes (e.g. cramp-fasciculation syndrome, Isaacs syndrome and Morvan syndrome). RMD can be genetically determined (CAV3 or PTRF mutations) or less commonly, immune-mediated. Voltage-gated potassium channel (VGKC)-complex autoantibodies are known to cause PNH syndrome. Dr. Liewluck is interested in the autoimmune basis and treatment of RMD and PNH syndromes.

Congenital myasthenic syndrome (CMS) is a genetically heterogeneous group of primary neuromuscular junction disorders. Most CMS patients develop fatigue and limb, ocular or bulbar weakness in their childhood; however, some may have adult-onset symptoms, which are clinically indistinguishable from patients with seronegative myasthenia gravis. Pyridostigmine (Mestinon) is a standard treatment for seropositive and seronegative myasthenia gravis, but it may be ineffective or worsen myasthenic symptoms in some CMS patients. Dr. Liewluck is interested in albuterol therapy in CMS patients who do not respond or respond poorly to Pyridostigmine. He and his former mentor, Dr. Andrew G. Engel, have recently reported the beneficial effects of albuterol in CMS patients due to endplate acetylcholinesterase deficiency and patients with Dok-7 myasthenia.

Edward H. Maa, MDDr. Maa is interested in treating medically and surgically refractory epilepsies. He is involved with clinical trials involving the antiepileptic drug development pipeline, but has specific interests in novel therapies including bumetanide and other diuretics, as well as cannabidiol and other phytocompounds used in the treatment of epilepsy. He is currently investigating the use of acupuncture for the treatment of non-epileptic seizures, and has had a long standing interest in the effects of high altitude and patients with epilepsy as well as new onset seizures in travelers to high altitude environments.

Ravi Mahalingam, PhDDr. Mahalingam’s laboratory studies varicella pathogenesis and latency and reactivation. Studies include the use of state-of-the-art technologies such as polymerase chain reaction, cDNA analysis and multiplex PCR analysis to study varicella transcription during primary infection as well as reactivation. Other studies include the role of cell-mediated immunity in the regulation of varicella latency and reactivation. A bacmid-based approach is also used to generate mutant varicella virus in an animal model.Finally, the laboratory uses diagnostic tools to understand neurological complications of zoster including postherpetic neuralgia.

Augusto A. Miravalle, MDDr. Miravalle is currently involved as Principle Investigator or Sub Investigator in multiple clinical trials at the University of Colorado, with participation in additional studies in the near future. Many of these studies involve novel immunotherapies as well as cutting edge therapeutic approaches for the treatment of MS. Dr. Miravalle has a particular interest in imaging studies evaluating early detectors for future disability in MS patients. He is active in the local, regional and international community, lecturing frequently in the United States and Europe.

Principal Investigators N-R

Maria A. Nagel, MDDr. Nagel specializes in neurovirology and studies how varicella zoster virus (VZV), which causes chicken pox and shingles, causes stroke. Her clinical studies include defining the frequency of VZV in patients with stroke, giant cell arteritis, and atypical facial pain. Her basic science studies focuses on the role of purinergic signaling and inflammation on VZV-induced pathological vascular remodeling.

Douglas E. Ney, MDDr. Ney’s clinical research focuses on innovative treatments including novel chemotherapeutic agents as well as targeted agents for the treatment of malignant glioma. His research interests also include new treatments and outcomes for patients with primary central nervous system lymphoma.

Chantal O'Brien, MDDr. O’Brien is currently involved as an Investigator in the Epilepsy Surgery Quality Improvement project and Sub Investigator in multiple industry sponsored clinical trials of novel anti-epileptics at the University of Colorado.

Debra O'Reilly, MS, PA-CDebra O’Reilly, PA-C is interested in clinical trials for the treatment of ALS. She is actively involved in a trial investigating the use of diaphragmatic stimulation to assist ventilation in patients with ALS. She is also working on a quality improvement project to address and treat depression in patients with neuromuscular disease.

Gregory P. Owens, PhDMultiple sclerosis (MS) is a CNS inflammatory disease of unknown cause.Dr. Owens’ research investigates the role of B cell immunity in the pathogenesis of MS.To better understand the nature of this response, they have used fluorescence-activated cell sorting and single cell PCR to analyze the B and plasma cell populations infiltrating the CNS of MS patients. The features of the B cell repertoire are indicative of a targeted and antigen driven response in MS. They have generated a panel of monoclonal recombinant antibodies from plasma cell clones identified in MS CSF and are using recombinant antibodies for immunological screening to identify disease relevant MS antigens.

Scott Pearson, MS, PA-CScott has a special interest in the clinical trials investigating novel therapeutic agents for the treatment of intractable epilepsy. He currently is a sub investigator on several clinic trials at the University of Colorado Hospital.

Victoria S. Pelak, MDDr. Pelak’s research investigates cortical visual processing, with a particular interest in the effects of aging and dementia on visual motion processing. She is exploring new methods to diagnose and track cortical visual dysfunction in early Alzheimer’s disease (AD). Traditionally, it is believed that visual processing deficits occur in the middle or late stages of AD. Recent studies from her Visual Perception Laboratory have demonstrated that visual processing deficits (as detected by a novel virtual task of kinetopsic 3D object processing developed by her research group) may be readily detectable in the very early stages of AD; this may have implications for predicting progression from mild memory impairment to AD. Additional ongoing investigations include studies of the effects of testosterone on visual motion/object/spatial processing and studies of visual hallucinations associated with degenerative disorders and vision loss. Methods of assessment include psychophysical testing using immersive virtual reality technology in her Visual Perception Laboratory and functional MRI techniques at the UCDSOM Brain Imaging Center

Sharon N. Poisson, MDDr. Poisson’s research focuses on etiology, prevention and treatment of transient ischemic attack (TIA) and stroke. She previously conducted research evaluating gender roles in the treatment of carotid stenosis in TIA, as well as the role of intracranial large vessel stenoses in TIA. She has a specific interest in the increasing trends of ischemic stroke in young adults, and is studying the role of atherosclerotic risk factors and race as potential causes of this trend. In addition, she has an interest in the quality of hospital care of patients with ischemic and hemorrhagic stroke.

Huntington Potter, PhDOur current research is devoted to laboratory and clinical investigation of neurodegenerative diseases, particularly Alzheimer’s disease (AD) and trisomy 21/Down syndrome (DS), which also induces AD by age 40. We hypothesized and showed that AD patients develop trisomy 21 and other aneuploidy cells, including neurons, during the course of their life and thus that AD is a mosaic form of DS. We recently found the mechanism by which aneuploidy develops in AD: the Ab peptide inhibits certain microtubule based kinesin motor proteins and thus prevents the transport of key cellular components, including vesicles, chromosomes, and microtubules themselves to their proper locations in the cell. As a result, dividing cells mis-segregate their chromosomes, generating aneuploid, including trisomy 21 cells in AD patients, cells in culture, and transgenic AD mice. Neurons also fail to localize neurotrophin and neurotransmitter receptors to the cell surface, resulting in the poor neuroplasticity. We have also found aneuploid neurons and other cells in patients and mouse models of Niemann Pick C and Fronto-Temporal Dementia, suggesting that chromosome mis-segregation may underlie many different forms of neurodegeneration. We are currently investigating the mechanism of chromosome mis-segregation and searching for means to prevent or reverse it. We also hypothesized that rheumatoid arthritis patients, who seldom develop AD release an endogenous protective molecule and showed that GMCSF and GCSF, over produced in RA, reversed AD pathology and cognitive deficits in a mouse model of AD. We are currently carrying out a clinical trial to test the safety and efficacy of human GMCSF (Leukine) in AD patients and have proposed a similar trial in DS.

Jeff Reynek, NPMr. Reynek is interested in research about the impact of headaches on daily life, with a focus on the diagnosis and management of head pain conditions.

Steven P. Ringel, MDDr. Ringel’s current investigative activities focus heavily on quality, safety and effectiveness studies. He has organized department-wide inpatient and ambulatory performance improvement projects and is assisting each subspecialty section of the department in the development of quality and safety projects. He continues to be involved in multi-university therapeutic trials in ALS. A current trial involves testing the efficacy of diaphragmatic stimulation to assist ventilation in ALS.

Principal Investigators S-Z

Lauren C. Seeberger, MDDr. Seeberger has conducted over 80 clinical trials for the advancement of treatments in movement disorders. Her research has involved patients with Parkinson’s disease, Huntington’s disease, Essential tremor, Dystonia, Tics and Restless Legs Syndrome. Dr. Seeberger has a strong interest in the use of rehabilitation in chronic disease.

Teri L. Schreiner, MD, MPHDr. Schreiner's research interests include genetic and environmental triggers of pediatric multiple sclerosis, immunotherapies for multiple sclerosis (MS) patients, and quality of life in pediatric patients with demyelinating diseases. In collaboration with others on campus, she also studies biomarkers of disease activity in MS.

Archana A. Shrestha, MDDr. Shrestha studies medically refractory epilepsy and epilepsy surgery. She also is interested in women’s issues in epilepsy and the influence of female hormones on seizures and epilepsy. ICU continuous EEG monitoring. Epilepsy in developing countries.

Jennifer Simpson, MDDr. Simpson has multiple quality improvement projects, in both the inpatient and outpatient settings. She has outpatient initiatives that help to reduce admissions and improve patient experience in clinic. On the inpatient side, she is working to improve efficiency and timeliness of acute stroke treatment. She is also the local principal investigator for a national trial involving patients with transient ischemic attack.

John R Sladek, Jr. Ph.DDr. Sladek’s laboratory, since his early publications on the chemical neuroanatomy of mammalian brain, has focused on the unique distribution of the histologically identifiable monoamine neurotransmitters, especially dopamine, norepinephrine, serotonin as well as peptidergic neurons of the hypothalamus including vasopressin, oxytocin, LHRH and others. His laboratory developed dual localization techniques that permitted detailed studies in higher order primates. His interests in the role these neurotransmitters played in normal brain function led to novel investigations during development and aging that suggested functional interactions between specific systems. In 1980, his pivotal publication in Science demonstrated that fetal neurons could be transplanted to the brain of a genetic mutant rat that that was incapable of producing vasopressin and that grafted fetal neurons could survive, integrate with the host brain and restore a lost neural function. This lead to new and continuing studies on the potential for fetal dopamine neurons to restore motor activity in a primate model of Parkinson’s disease. His proof of principle findings led to the first clinical trials in parkinson patients and in recent years have been extended to incorporate human neural stem cells in the experimental protocols. Professor Sladek continues his exploration of the ability of the primate brain to respond to various neural repair strategies including the potential for induction of neurogenesis in response to injury. His work has been supported continuously by NIH, NSF and several foundations since 1974. Dr. Sladek is the founding President of the American Society for Neural Therapy and Repair, has presented his work at over 350 invited meetings and seminars and is Editor-in-Chief Emeritus of the journal, Experimental Neurology.

Mark C. Spitz, MDDr. Spitz’ clinical research includes epilepsy that begins in the elderly, psychiatric aspects of epilepsy and physical injuries that occur from seizures. Dr. Spitz is involved in several ongoing medication trials.

Laura A. Strom, MDDr. Strom is currently working on investigator initiated clinical research with two different areas of interest. She continues to be very interested in the influence on patients with medically refractory epilepsy of the autonomic nervous system. She is working with resident physician, Dr. Peter Bergmann on a project to investigate how heart rate variability may predict changes in heart rate during seizure activity. Her second area of active interest is in the impact on epilepsy of hormones. She is working with another resident, Dr. Danielle McDermott to develop a research project looking at fluctuations in sex hormone levels in patient with medically refractory epilepsy. In addition to clinical research, Dr. Strom is primary investigator for several industry sponsored clinical trials of novel anti-epileptics as well as novel uses for anti-epileptic drugs which are already on the market.

Jean Tsai, MDDr. Tsai is interested in the regulation of sleep and the biological effects of sleep. The interaction between sleep disorders and neurological diseases, such as that between sleep apnea and stroke, RBD and neurodegenerative disorders, and RLS and movement disorders, is an area of particular importance.

Kenneth L. Tyler, MDDr. Tyler’s laboratory uses both in vivo and in vitro models to study the molecular and genetic basis of viral pathogenesis and viral-induced cell death. A major research effort investigates the mechanisms by which viruses induce apoptosis. Current projects include: (1) investigating the role played by specific viral genes and the proteins they encode in triggering apoptosis; (2) identifying the role of apoptosis in mediating virus-induced tissue injury in various target organs, including the CNS in vivo (3) defining the cellular pathways by which apoptosis is induced in virus- infected cells. Studies of cellular mechanisms of apoptosis currently involve investigations into virus-induced alterations in MAP kinase and other signal transduction pathways, transcriptional activators including c-Jun and NF-kB, the use of genomic microarray and proteomic technology to identify genes and proteins altered during viral infection of target cells, and identifying death-receptor and mitochondrial caspase signaling pathways. Further details about specific personnel and their projects can be found on the Tyler Lab web site. Ongoing clinical research includes projects sponsored by the Collaborative Antiviral Study Group, the AIDS Clinical Trials Group, and the Neurologic AIDS Research Consortium in areas of West Nile virus infection, herpes encephalitis, and the neurological complications of HIV infection.

Timothy L. Vollmer, MDDr. Vollmer is the Director of Neurosciences Clinical Research. He is currently involved as Principles Investigator of Sub Investigator in 26 clinical trials in multiples sclerosis at the University of Colorado, with participation in additional studies in the near future. Many of these studies involve immunotherapies for the treatment of this disease. Dr. Vollmer has a particular interest in investigator initiated clinical trials focusing on optimizing current therapies and combinations of therapies. To date, Dr. Vollmer has completed over 100 clinical studies in MS. He is active in the local, regional and international communities conducting research in MS. He lectures frequently in the United States and Europe.

Ashish A. Vyas, MDDr. Ashish has research interest in continuous EEG monitoring in critically ill patient and in patients with status epilepticus, and refinement of techniques for source localization in focal epilepsy. He is also interested in clinical drug trials and outcome studies in epilepsy and use of compressed spectral data of improvement of techniques of quantitative electroencepha-lography to facilitate easy detection. Apart from epilepsy, study of autonomic dysfunction in parkinson patients is another research area of his interest.

Anastacia Wall, PA-CMs. Wall's research interests include immunotherapies for multiple sclerosis (MS) patients and quality of life in patients with demyelinating diseases.

Jonathan H. Woodcock, MDDr. Woodcock directs clinical research projects in dementia including medication trials in Alzheimer’s disease, cognitive and functional deficits in adults with Down syndrome, and assessment and management of behavioral syndromes in dementia.

W. Michael Zawada, PhDWe seek to discover universal pathogenic mechanisms underlying the earliest stages of neurodegeneration and target these causal entities in an attempt to develop disease-modifying treatments across a spectrum of neurodegenerative conditions. In particular, using patient brain tissues as well as mouse models, we have highlighted the role of the brain renin-angiotensin system (RAS) in initiation and maintenance of neurodegeneration in Parkinson’s and in Alzheimer’s, where the loss of control over RAS-mediated signaling in neurons and glia promulgates neuronal stress, dysfunction, and death. In this vein, we discovered that neurons generate all of the constituent proteins of RAS that act to modulate signaling cascades involving NADPH oxidase (Nox)-driven neurooxidation, neuroinflammation, neurogenesis, neurotransmission, and proteostasis. These previously unrecognized functions of intraneuronal RAS challenge earlier hypotheses attempting to describe early triggers of degenerative processes in the brain. At present, we are investigating how therapeutic modifiers of RAS-linked signaling cascades, such as angiotensin receptor blockers (e.g., telmisartan), might interfere with injurious processes and promote neuronal resilience in models of degenerative conditions such as Parkinson’s, Alzheimer’s, and Down’s syndrome.

Varicella Zoster Virus (VZV) is a neurotropic alphaherpes virus. The primary infection by VZV is chicken pox (Varicella), followed by the virus going dormant (latent) in the sensory, cranial and autonomic ganglia along the entire neuraxis. Viral reactivation, mainly in the elderly, can cause zoster or shingles, which can also result in postherpetic neuralgia, meningoencephalitis (inflammation of the brain), myelopathy (spinal cord infection) and sometimes blindness. We are currently investigating the molecular mechanisms responsible for establishment of viral latency, and reactivation. Techniques such as qPCR and next generation sequencing are currently being employed to monitor viral DNA replication and transcription in the latently infected human ganglia. Understanding the state of viral transcription in these latently infected ganglia will subsequently help us design therapeutic agents against viral reactivation.

Varicella zoster virus is a member of the neurotropic alphaherpesvirus family. During primary infection, the host develops varicella (chicken pox) after which the virus establishes latency in sensory neurons along the entire neuraxis. As the host’s cell-mediated immunity declines with advancing age, VZV reactivates to cause zoster (shingles) and may also cause meningoencephalitis (brain infection), vasculopathy (stroke), myelopathy (spinal cord infection) and ocular disease (eye infection). Using an in vitro model of cultured human neurons which are infected with VZV, studies are designed to understand the molecular events leading to, and required for, establishment of viral latency. Viral latency is monitored using qPCR, immunofluorescence and next generation sequencing (NGS) to determine the state of viral DNA, levels of viral protein expression and extent of viral transcription, respectively, in the infected neurons.

Multiple Sclerosis (MS) is the most common non-traumatic cause of neurological disability in young adults, presenting an urgent public health challenge. To better treat MS, disease mechanisms must be more thoroughly understood, so therapies can be developed toward relevant molecular targets. Evidence has accumulated indicating significant roles for the B cell response in MS. Plasma cells persistently secrete Immunoglobulin G (IgG) within the central nervous system (CNS) of MS patients, likely contributing to the neurological damage which occurs in MS. MS IgG-mediated damage has not been fully characterized, and novel IgG antigenic targets need to be identified.

Dr. Blauth works in the laboratory of Dr. Gregory P. Owens, and the goal of his research is to delineate the cellular damage and corresponding functional deficiencies that IgG derived from MS plasma cells cause to the CNS. Paired with Dr. Owens’ MS antigenic target discovery research, these studies will lead to a greater understanding of disease mechanisms in MS, and provide the groundwork for the development of novel MS therapies.

Dr. Zhuang has been investigating the mechanisms of reovirus-induced cell death both in vitro and in vivo during reovirus encephalitis. One of the goals of his studies is the identification of novel cellular targets with potential therapeutic applicability for viral encephalitis. Dr. Zhuang and his colleagues demonstrated that Daxx up-regulation within the cytoplasm of reovirus-infected cells is mediated by interferon and contributes to apoptosis. In most cell types, including neurons within the brain, mitochondrial apoptotic signaling pathways are activated and appear to be required for pathogenesis. Dr. Zhuang currently focuses on studying mitochondrial apoptotic activity of p53 in neuron upon reovirus infection.